ASBMB Members in Industry

BY NICK ZAGORSKI

Although a majority of the American Society for Biochemistry and Molecular Biology community hails from the world of academia, the society also has a rich and diverse set of members in the industry sector. In this special Science Focus, we profile just a few of these “industrious” individuals to showcase the scope of research being carried out in this arena: Bruce Morimoto, John Purcell, Jay Slack and Patricia Weber. (Titled "ASBMB’s Industrial Revolution" in print version.)

Bruce Morimoto

Vice President for Drug Development

Not long ago, Bruce Morimoto was presenting research at a conference in which the speaker ahead of him described his 400-employee biotech firm as a “small company.” When it was Morimoto’s turn to speak, the V.P. for drug development at 20-member Allon wryly noted, “Well, if they’re small, we must be micro.”

Not that Morimoto would want it any other way. “Working at a really small company is much like running a lab in academia,” he says. “There’s a real sense of ownership, and everyone on the team is empowered to do whatever it takes to get the job done; that kind of environment fits my personality well.”

At Allon, which specializes in combating neurodegenerative diseases, Morimoto’s job entails moving drugs from discovery to market, which means he oversees a little bit of everything, from basic chemistry to manufacturing.

Morimoto never envisioned having such responsibilities when he was an undergraduate at the University of California, Los Angeles; in fact, back then, he believed his only options for pursuing his fondness of science were to become a physician or engineer.

But, his chemistry lab teaching assistant introduced him to undergraduate research, and his eyes opened up to a whole new world of possibilities.

He continued on the academic path, first getting his doctorate at UCLA (finishing the undergraduate project he started), then moving on to a postdoctoral fellowship with Daniel Koshland at the University of California, Berkeley and finally a faculty position at Purdue University.

Life seemed settled, but a few years into his professorship, Morimoto headed to the San Francisco Bay Area for a two-day consulting trip with a biotech company. Once he was done, the company surprised him by offering him a position.

While moving closer to the ocean was appealing to the native Angeleno, the thought of switching to industry was nerve-wracking; however, when Morimoto was given the chance to bring along his whole research group so his students could finish out their projects, he was sold. “That gave me a nice transition period to wind down my basic research and avoid any potential culture shock.”

Morimoto began industry life working in drug discovery research, but over the years, as he gained experience and moved around, he began shifting more to the applied research and product development side of things, leaving his lab coat behind.

Because of the size of the company, Allon does not handle the development process in-house; rather, it is one of many biotech companies that have embraced the “virtual drug development” model, outsourcing the various stages of development to contract labs across North America and Europe while managing the overall flow.

Currently, the major company effort involves their lead drug davunetide, which has demonstrated efficacy for some forms of cognitive impairment. Allon is beginning clinical trials for an orphan disease known as progressive supranuclear palsy, or PSP.

“A major neurodegenerative disease like Alzheimer’s is just too big for a small company like Allon,” Morimoto explains, “but we can use PSP, which is much rarer, as a proxy, because it displays pathology of entangled Tau protein, which happens to be one of the two major pathologies of Alzheimer’s.”

“Therefore, once we get data and approval of our drug for PSP, it opens up the market for us to partner with a larger company and move the drug to more prevalent diseases.”

Morimoto notes that in this regard, Allon serves as an excellent bridge between basic academic research and major industry. “We have the freedom to pursue scientific avenues that big pharma typically overlook,” he says, “which we can then translate to a form that appeals to large companies.”

As for any concerns that a large biotech firm may end up buying out Allon to remove the middle man? “Well, that possibility comes with any small company,” says Morimoto, “but if you look at recent news, with Pfizer buying Wyeth for example, there’s no stability guarantee in a big company either, so we’re not going to get too worried about it.”

John Purcell

Ask John Purcell what his favorite part of working for a major global company like Monsanto is, and you get a surprising answer. It’s not the access to top-notch scientific resources like the company’s discovery labs and sequencing capabilities, or the incredible pool of talented scientists at the company, though he notes those are great.

For Purcell, currently the vice president of global technology development in Monsanto’s vegetable seeds division, his favorite moments are the ones literally in the field, walking with farmers to see how Monsanto’s crops are performing.

“I’ve met with farmers and walked in plots ranging from small vegetable gardens to giant corn fields on every continent except Antarctica.” says Purcell, who’s loved the outdoors since his childhood days. “And I’ve learned that farmers everywhere share the same fundamental desires; they want to produce a high quality product and use their resources as efficiently as possible.”

It’s a desire Purcell has been trying to help materialize for more than 20 years at Monsanto, during which time he has been involved in almost every stage of the agricultural biotechnology process, from discovery and development to marketing and monitoring.

And, it’s a desire shared by his employer; Purcell recalls his first visit to Monsanto’s headquarters in St. Louis back in 1989 when he was looking for a position and toured the company’s then-new life sciences research center.

“From a biologist’s perspective, it certainly looked like nirvana,” Purcell notes, “but, at the same time, it showed me that this company had made a major investment to change the way we think about agriculture, namely how we can use biological tools to solve problems typically managed by chemical means.”

Purcell began his work to find such tools in Monsanto’s insect control division, which built on his existing research strengths; as a graduate student at the University of Massachusetts Amherst, he had studied insect biochemistry in Jack Nordin’s lab, and later he did a postdoc at the U.S. Department of Agriculture, where he studied nematode biology and potential control mechanisms.

Over the next decade, he helped in the development of many breakthroughs, perhaps most notably the engineering of Bt crops, which are fortified with Bacillus thuringiensis toxins, designed to kill specific insect pests while remaining safe for humans and other beneficial species. Purcell then proceeded with stints in both the corn and cotton divisions, before settling in last year to his position in the vegetable seeds division.

His current efforts follow the same overall mission statement of helping farmers achieve the most efficient yields, but advances in technology have enabled him to expand his scope. Monsanto’s approaches to crop biotechnology are from an agronomics perspective, primarily focusing on helping farmers control problems like weeds, pests, nutrients and water (Purcell notes the latter will be an especially significant concern in the coming years), but now they have begun to explore quality in addition to yield.

“In the vegetable division, we’ve started to use advanced breeding techniques and our increased knowledge of molecular markers to try to improve the appealing characteristics of our products, such as taste,” he says. He cites the recent advancement of developing a sweet onion with a milder flavor, for use in salads and sandwiches, which can be grown in season in the U.S. and stored and sold all winter long.

Purcell notes that it is important to broaden the research effort because global institutes like Monsanto face challenges that smaller companies don’t. “One issue with being well known is that people expect a lot out of you, and you have to continually earn their trust.”

Fortunately, in that regard, Monsanto has one more advantage: Although taste may be varied, food is a constant. “There always will be strong demand for our products, because people always will need to eat.”

Jay Slack

In 1999, groundbreaking research from Charles Zuker’s lab group identified the first two genes encoding taste receptors— T1R and T2R. Although the discovery of these long-speculated taste receptors was notable for its intellectual advancements, it also opened up a whole new commercial research sector.

Jay Slack found himself in the right place at the right time to reap the benefits.

Slack was finishing up his postdoctoral work on the genetics of the immune system with John Monaco at the University of Cincinnati, and was considering a career move. “The department where I was working had just hired three new faculty members, so I witnessed firsthand the scientific pain associated with trying to get tenure in academia,” he says. “So, I decided to maybe carve out my niche somewhere in industry.”

Having done his graduate training in pharmacology (focusing on calcium signaling in the heart), Slack initially explored pharmaceutical options, but, a chance conversation with the head of the transgenic animal facility revealed that a local company called Givaudan Flavors was looking to build on Zuker’s findings and establish an in-house taste receptor research group.

“I knew very little about the business of flavors, but working for Givaudan appealed to me because the science was interesting, and it was an emerging field,” he notes. “But what really sold it for me was that my daughter was taking antibiotics and absolutely hated their taste, so I thought instead of working for 20 years and maybe getting a drug to market, I could try to make existing drugs taste better and help patients immediately.”

And, although Slack and Givaudan have not quite reached that goal yet, they are making solid progress; just a few months ago, his group identified an inhibitor that blocks the bitter aftertaste associated with artificial sweeteners, which they can now use as a template to find future compounds that can make bitter pills a little easier to swallow.

But that work is just one aspect of Givaudan’s goals, which makes Slack’s work all the more enjoyable. “Our group is active in all the classical areas of taste, from sweet to savory, as well as in taste chemesthetics, which includes sensations such as pungency or cooling.” As an example, he notes that his group recently has developed a high potency analog of menthol that produces a cooling sensation that lasts for more than two hours, so you can have that fresh breath feeling from breakfast to lunch.

In addition, he has the freedom to pursue basic research pursuits. One area he’s particularly interested in involves the genetic variability of taste perception, at both the individual and population levels. He hopes to understand the mechanisms underlying the variation, whether it occurs in the receptor genes or in downstream pathways, and whether this variation influences behavior.

“Scientists have continued to identify more and more taste receptors,” he says, “and they’ve even begun finding them in non-taste cells, places like the gut, nasal cavity and even the brain. It’s possible that these internal taste receptors are linked to hormonal signals and mediate hunger or satiety.”

One thing that won’t be satiated any time soon, however, is the opportunities in the taste industry. Although this formerly orphan area of research has exploded over the past decade, it still remains a relatively new field with many unexplored avenues. “Taste research involves numerous fields of study, including organic chemistry, analytical chemistry, natural products, pharmacology and enzymology,” Slack says, “so, it definitely provides numerous options for young scientists.”

Patricia Weber

Re-entering the work force after taking an extended leave can be a challenging proposition. Such was the case with Patricia Weber, who took a break from a long and fruitful career in the industry sector in 2001 to spend more time with her family (though she remained active by doing scientific consulting and serving on the editorial boards of the Journal of Biological Chemistry and Faculty of 1000).

A few years later, with her younger son now ready for college, Weber felt an itch to resume her research pursuits. Considering her options, she decided to try something a little bold; teaming up with a former co-worker, Ray Salemme, she formed a new company called Imiplex, billed as offering nanosolutions for the 21st century.

“Nanotechnology is a relatively young field, especially protein-based nanotechnology, which is our focus,” Weber notes. But, it’s also a field that has tremendous growth potential in many disciplines (as noted in the June issue of ASBMB Today).

The idea behind Imiplex, which was started with the help of a pair of Phase 1 Small Business Innovation Research grants, is to design modular molecular protein nanostructures that can self-assemble into a variety of architectures. Weber and her team use highly stable proteins taken from thermophiles as the starting point, making them easier to manipulate and derivatize while retaining their native structures.

Once complete, Imiplex will sell both the individual modules of the platform and the technology required to assemble the supramolecular structures. Customers can purchase prefunctionalized modules or functionalize the components themselves, offering flexibility in how the technology is used.

Of course, Weber has her own visions and interests, and plans on making some specially designed products as well. “My personal interest is to help improve quality of life in developing countries, and thermostable nano-assemblies can be used outside of biological settings, so I see potential in areas like water purification.”

This type of endeavor brings together all of Weber’s previous biological expertise, built up over 25 years in academia and industry. It all began with her doctorate at the University of Arizona in 1979, followed by a postdoc with Nobel-winning crystallographer Thomas Steitz at Yale University. Afterwards, she joined Genex Corp. where she worked on one of the first teams involved in engineering industrial enzymes, and then took positions at DuPont and Schering-Plough, where she carried out structure-based drug design.

“I often point out to students that during most of my career, I remained at the bench,” Weber says, “because I think that’s an advantage of industry if you like the hands-on aspect of doing experiments.”

Weber certainly will need to do a lot of hands-on work at Imiplex, a true start-up employing a handful of staff and collaborators. The company is currently in the proof-of-concept stage, trying to demonstrate that these modular platforms can self-assemble under a variety of conditions.

“The work has been progressing well,” Weber notes, “so I’m hopeful that within the next few months, we will be ready for the next stage, when we can bring in venture funding to help us grow the company and increase production.”

Weber always has been a positive person, and it’s important to keep a positive attitude while nurturing a start-up; even with the combined knowledge and expertise Weber and Salemme bring to the operation, biotechnology is a tricky business that requires someone with a sense of adventure and fearlessness.

The right frame of mind helps too, which Weber definitely has. “My goals are to keep the company moving forward, create high technology jobs and eventually bring the benefits of nanotechnology to many people.”